Table.

Clinical findings for five patients with brentuximab vedotin-associated PML

	Hodgkin’s lymphoma	Hodgkin’s lymphoma4, 6	Hodgkin’s lymphoma	Cutaneous anaplastic T-cell lymphoma5	Stage IB Mycosis Fungoides
Clinical trial participant	Yes (5th PML case submitted to the FDA and the manufacturer- 11/2012)	Yes (1st PML case submitted to the manufacturer and to the FDA- 7/04/2011)	Yes (3rd PML case submitted to manufacturer and FDA- 11-15-2011)	No (2nd PML case submitted to the FDA- 10/2011)	No (4th PML case submitted to the manufacturer and to the FDA- 3/29/2012)
Age at time of PML diagnosis, gender	51, male	47, male	50, male	38, female	72, female
Speech/ mental status	Difficulty with word finding; confusion; forgetfulness over several weeks	Dysarthria; encephalopathy	Dysarthria	Mixed non-fluent aphasia, apraxia	Poor short term memory; confusion
Motor	Normal	Left hemiparesis; Impaired coordination	Right leg weakness and difficulty writing with right arm weakness	Mildly decreased strength in all extremities	Generalized weakness
Gait	Normal	Impaired due to hemiparesis	Impaired due to right leg weakness	Ataxia- requiring one person assist	Not tested
Vision	Normal	Left-sided hemianopsia	Normal	Normal	Normal
Differential diagnosis at time of PML presentation	PML or viral encephalitis- based on clinical and MRI findings	Ischemic stroke	Subacute CNS ischemia or progression of lymphoma	Metastatic brain lesions	PML- based on clinical findings and MRI findings
Detection of JCV	CSF- JCV DNA detected by PCR	CSF- JCV DNA detected by PCR in second LP, No JCV detected in initial LP.	Spinal cord lesion biopsy- initially negative for JC virus. Later evaluation of the sample by Genzyme detected JC virus. JC virus not detected in CSF from two lumbar punctures.	Brain biopsy- JCV detected by immunohistochemistry.	Brain autopsy with JCV detected by in situ hybridization. JCV not detected in CSF.
MRI	Multifocal areas of non-enhancing T2 white matter; greatest in the anterior/inferior right frontal lobe. Additional areas of subcortical T2 hyperintensity in bilateral temporal lobes.	T2 hyperintense lesion in right cerebral hemisphere with well circumscribed enhancing lesions in right parietal lobe.	Ill-defined abnormal T2 hyperintensity involving left superior cerebellar peduncle.	Multifocal white matter lesions left more than right hemisphere	Asymmetric T1 hypointense and T2 hyperintense lesions of the frontal white matter
Other illnesses	Thyroid cancer; thyroidectomy; chronic lymphopenia	Diet controlled diabetes mellitus; depression	Epilepsy; migraine headaches	Severe eczema	None
Prior medications (between 9–12 years prior to PML)			ABVD1; radiation to abdomen and pelvis	Topical steroid creams
Prior Medications (between 5–8 years prior to PML)		Broad-field radiotherapy and ABVD1	ICE4 (for relapse)- with partial response; BEAM; autologous stem cell transplant;	Topical steroid creams
Between 3 and 4 years prior to PML		ESHAP2, (for relapse); BEAM3, autologous stem cell transplant	Localized radiation therapy to right neck (for second recurrence- nodular sclerosing Hodgkins disease)	Topical steroid creams	Topical corticosteroids, nitrogen mustard, phototherapy, interferon alfa-2b
Between 1 and 2 years prior to PML		gemcitabine, vinorelbine, and liposomal doxorubicin	None	Methotrexate, Targretin, denileukin diftitox, interferon gamma-1b; interferon alfa-2b	Topical corticosteroids, nitrogen mustard, phototherapy, interferon alfa-2b
< 1 year prior to brentuximab vedotin	ABVD1			Targretin, denileukin diftitox, interferon gamma-1b; interferon alfa-2b; vorinostat; praletrexate	Bexarotene, radiation therapy, romidepsin
Following brentuximab vedotin	Autologous stem cell transplantation; ICE4		Augmented ICE4 (two cycles)	Prednisone
# of doses of brentuximab vedotin and clinical response	6 doses (1.2 mg/kg q week). Total of two cycles of three doses. PET scan became negative following last brentuximab vedotin dose.	3 doses (1.8 mg/kg) – 21 days apart (PET showed favorable response to therapy).	5 doses (1.8 mg/kg)- clinical trial participant- withdrawn due to peripheral neuropathy; 2 additional doses (1.2 mg/kg)	2 doses (1.8 mg/kg q 3 weeks)- (one cycle). Disappearance of skin tumors.	Three doses (significant response of skin lesions)
Subsequent course	Progressive neurological deterioration. Died eight weeks after PML diagnosis.	Progressive neurological deterioration and worsening MRI. Died in hospice 8 weeks after PML diagnosis.	Progressive neurological deterioration and worsening MRI findings; T1–T2 and T8–T9 intramedullary lesions; Radiation therapy (3000 Gy) to T1–T2 lesion and corticosteroids. Paraplegia developed. Died in hospice six weeks after PML diagnosis and 20 weeks after first brentuximab vedotin treatment.	Neurological and radiological improvement- maintained on prednisone 50 mg orally/day for a year. Upon discontinuing corticosteroids, a new enhancing brain lesion developed. The patient restarted prednisone 20 mg orally/day with resolution of this lesion and no evidence for new lesions.	Progressive neurological deterioration. Died in hospice 15 weeks after first brentuximab vedotin treatment.
Time from first brentuximab vedotin to main PML symptoms	36 weeks. Six months following the autoSCT- confusion; forgetfulness; difficulty finding words	3 weeks- impaired coordination, left > right dysiadokinesis, slurred speech, left sided hemianopsia and visual neglect, left hemiparesis, and left central facial paresis.	24 weeks; speech changes; incoordination of right hand (poor penmanship) and right lower extremity weakness.	3 weeks- mixed aphasia, inability to read, and unsteady gait.	7 weeks- disorientation, poor short-term memory, and weakness

¹doxorubicin, bleomycin, vinblastine, and dacarbazine;

²etoposide, methylprednisolone, cytarabine, cisplatin;

³carmustine, etoposide, cytarabine and melphalan;

⁴ifosfamide, carboplatin,